This application constitutes the fifth competitive renewal of The Mount Sinai School of Medicine Alzheimer's Disease Research Center. We have used the strengths of our well established center to address the new vision of the NIA Center program. We have proposed standardized assessment to be used at all our sites and the EITC will assist us with developing procedures manual, training materials and certification methods to insure that the evaluations can be reliably collected from a range of research staff. The newly established Data Management Core has been intimately involved in the development of the data collection instruments to insure that they can be readily entered into the data warehouse, that clinical and neuropathological information can be acct and integrated and that the extraction of the NACC data set can be accomplished seamlessly. This submission highlights our long standing accomplishments in clinical evaluation and neuropathological characterization of healthy elderly, mild cognitive impairment and early AD. In Project one we will integrate clinical and neuropathological to trace the earliest indicators of cognitive change in aging and dementia I n Projects 2 and 3, leading notions of potential etiologic mechanisms are explored in depth. In this renewal the following Cores and Projects are proposed: [unreadable] [unreadable] Administrative Core A (M. Sano) [unreadable] [unreadable] Clinical Research Support Core/ Elmhurst Satellite (D. Marin) [unreadable] [unreadable] Data Management Core C (V. Haroutunian) [unreadable] [unreadable] Neuropathology Core D (D. Perl) [unreadable] [unreadable] Education and Information Transfer Core E (M. Sano/M. Sewell) [unreadable] [unreadable] Project #1: Selective Neuronal Pathology in the Development of Dementia (P. Hof) [unreadable] [unreadable] Project #2: Identification and characterization of first messengers that regulate APP processing (J. Buxbaum) [unreadable] [unreadable] Project #3: PSI Regulates Cleavage and Function of EphrinB ligand and EphB Receptor (A.Georgakopoulos). [unreadable] [unreadable] CRITIIQUE: [unreadable] [unreadable] PRINCIPAL INVESTIGATOR [unreadable] [unreadable] Dr. Mary Sano, the new Principal Investigator of the Mt. Sinai Center, received her Ph.D. from City University of NY in Neuropsychology. She will replace Dr. Kenneth Davis, who is now the President and CEO of Mt. Sinai. [unreadable] [unreadable] Dr. Sano has devoted her career to the study of AD, and is a pioneer in the area of clinical trials and development of instrumentation in the area of AD neuropsychology. She has made significant contributions to the field. One of the most notable is the clinical trial of segeline and vitamin E for the treatment of AD, a successful study published in the New England Journal of Medicine. She has been a leader in the development of Spanish speaking instrument protocols, and has continued to collaborate and lead a variety of clinical trials. She is the principal investigator on a primary prevention trial to study effect of estrogen on conversion to dementia. She also leads a multi-center trial on Vitamin E and Down syndrome, and is the PI in the ADCS program to evaluate Simvastatin on the progression of AD. She has excellent organizational skills as evident from her leadership in the Vitamin E study, the organization of the Estrogen, and the Simvastatin trial. She works well with multiple investigators at the same time, and can be relied upon to accomplish her part in a Project in a timely manner. She has a great capacity to poly-task, and manages to meet multiple deadlines at the same time. [unreadable] [unreadable] Dr. Neil Kowal, who led the external advisory committee in March 2003, shortly after Dr. Sano had taken over the Mt. Sinai ADRC commented it was unanimous opinion of the board that he is exceptionally well suited for the new role as Director. She may have an exemplary record of accomplishment, and the Board is confident in her organizational and administrative skills. [unreadable] [unreadable] REVIEW OF INDIVIDUAL COMPONENETS [unreadable] [unreadable] CORE A: ADMINISTRATIVE CORE; Dr. Mary Sano [unreadable] [unreadable] DESCRIPTION (provided by applicant): The purpose of the Administrative Core of the Alzheimer's Disease Research Center is to maximize the productivity of the Projects and Cores of the Center by the coordination and integration of scientific, fiscal and clerical activities. The aims of the Core are [unreadable] [unreadable] To set the research directions of the ADRC. We will commit resources to these themes, including targeted initiatives for pilot Projects To direct the activities of the ADRC. We will continue to use our executive committee to accomplish the goals of the center and we will strengthen/create a structure to accomplish operational and fiscal administration of the grant. [unreadable] [unreadable] To provide the mechanisms for the review, revision and submission of pilot Projects each year. . [unreadable] [unreadable] To facilitate ADRC support for AD research that is not directly funded by the ADRC by making the Center's resources available to those studies. [unreadable] [unreadable] To facilitate interactions among Cores and Projects, as well among other ADCs, and AD based research and service groups. In this renewal we have planned several activities to stimulate interaction between clinical and basic scientist at several local institutions. In addition we have collaborated in several Projects submitted to NACC with other ADCs [unreadable] [unreadable] To foster the growth of new research and new researchers. The Administrative Core is committed to developing clinician and basic science investigators by providing training, mentoring opportunities and resources in the way of pilot funding to new researchers. [unreadable] [unreadable] The Core functions through frequent meetings with directors of other Cores and principal investigators of each Project, as well as through a series of internal and external advisory committees that meet regularly. [unreadable] [unreadable]